This project involves investigations of the role of cellular membranes in the functioning of nerve cells, in the hope that a more fundamental appreciation of these phenomena will lead to a more fruitful understanding of the basic processes involving in the physiology and pharmacology of the nervous system. The chief emphasis centers on two areas: (1) the molecular processes associated with the transport of sodium and potassium ions across nerve membranes, processes dependent on an enzyme, the (Na ions plus K ions)-dependent ATPase, which not only represent a major fraction of the brain's metabolic energy but also may be site of action of certain therapeutic agents; and (2) the processes involved in calcium transport and distribution in brain, both in vivo and in vitro, for calcium ions are intimately associated with the control of neural activity, both along the axon and at the synaptic endings where the release of neurotransmitters is specifically dependent on the availability of calcium.